CaltechAUTHORS
  A Caltech Library Service

A Facile Method for Separation of the Cryptic Methionine Sulfoxide Diastereomers, Structural Assignment and DFT Analysis

Raskatov, Jevgenij A. and Virgil, Scott and Lee, Hsiau-Wei and Henling, Lawrence M. and Chan, Ka and Kuhn, Ariel J. and Foley, Alejandro R. (2019) A Facile Method for Separation of the Cryptic Methionine Sulfoxide Diastereomers, Structural Assignment and DFT Analysis. Chemistry: a European Journal . ISSN 0947-6539. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20200103-100613520

[img] PDF - Accepted Version
See Usage Policy.

1120Kb
[img] MS Word - Supplemental Material
See Usage Policy.

1125Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20200103-100613520

Abstract

Methionine (Met) oxidation is an important biological redox node, with hundreds if not thousands of protein targets. The process yields methionine oxide (MetO). It renders the sulfur chiral, producing two distinct, diastereomerically related products. Despite the biological significance of Met oxidation, a reliable protocol to separate the resultant MetO diastereomers is currently lacking. This hampers our ability to make peptides and proteins that contain stereochemically defined MetO to then study their structural and functional properties. We have developed a facile method that uses supercritical CO₂ chromatography and allows obtaining both diastereomers in purities exceeding 99%. ¹H NMR spectra were correlated with X‐ray structural information. The stereochemical interconversion barrier at sulfur was calculated as 45.2 kcal/mol, highlighting the remarkable stereochemical stability of MetO sulfur chirality. Our protocol should open the road to synthesis and study of a wide variety of stereochemically defined MetO‐containing proteins and peptides.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/chem.201904848DOIArticle
ORCID:
AuthorORCID
Virgil, Scott0000-0001-8586-5641
Additional Information:© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Accepted manuscript online: 22 December 2019; Manuscript accepted: 20 December 2019; Manuscript revised: 18 December 2019; Manuscript received: 24 October 2019. JAR thanks UCSC for flexible start-up funds and a special research grant to study methionine oxidation. Dr. Indranil Chakraborty is gratefully acknowledged for assistance at early stages of the project. We also thank the late Mr. Stephen Hauskins and the UCSC computing team for help and support.
Funders:
Funding AgencyGrant Number
University of California, Santa CruzUNSPECIFIED
Subject Keywords:Amino Acids; Super-critical CO2 separation; Structural assignment; Sulfur chirality
Record Number:CaltechAUTHORS:20200103-100613520
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200103-100613520
Official Citation:Raskatov, J., Virgil, S., Lee, H., Henling, L., Chan, K., Kuhn, A. and Foley, A. (2019), A Facile Method for Separation of the Cryptic Methionine Sulfoxide Diastereomers, Structural Assignment and DFT Analysis. Chem. Eur. J.. Accepted Author Manuscript. doi:10.1002/chem.201904848
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100492
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Jan 2020 03:40
Last Modified:05 Jan 2020 03:40

Repository Staff Only: item control page